Hemangiosarcoma (HSA) is also known as angiosarcoma or malignant hemangioendothelioma.  It is a malignancy of the endothelial cells (lining cells) of blood vessels.  It is more common in dogs than in cats and can occur in multiple locations.  In dogs, it most commonly arises from the spleen and less commonly from liver, heart, and skin or subcutaneous tissues; and in cats it is found in cutaneous and abdominal locations (spleen, liver, intestine).   It is more frequently seen in middle-aged to older animals and German Shepherds, Golden Retrievers, and Labrador Retrievers are overrepresented in many studies.  The cause of HSA is unknown, although there is a documented increase in HSA  development in Beagles exposed to ionizing radiation. Cutaneous HSA is more common in dogs with minimal pigmentation and thin hair coats suggesting UV light exposure as a possible cause.  There is increasing evidence that dysregulation of molecular pathways governing angiogenesis may be important in the cause of HSA (Withrow & MacEwen’s Small Animal Clinical Oncology, 4th ed.).

  In dogs, most HSAs are aggressive with a high rate of metastasis to other organs. In cats, it tends to be a less aggressive disease.

  While HSA is the most common splenic cancer diagnosed, it is important to remember that not all splenic masses are HSA.  We follow what is called the “double two thirds rule” which means approximately 2/3 of dogs with splenic masses will have malignant tumors and approximately 2/3 of those malignant tumors will be diagnosed as  HSA.  This means that approximately 43% of masses found in dogs spleens are ultimately diagnosed as HSA.  The remainder are benign or lower grade malignancies. 

What are the symptoms of HSA?

For most types of HSA, except those found in the skin, symptoms are often vague and non-specific.  In many cases, there are no pre-emptive clinical symptoms until an acute bleed from the tumor occurs and patients become spontaneously weak or actually collapse.   In patients with acute bleeds, the diagnosis is usually made at the time of an emergency surgery to remove a ruptured splenic tumor.  Dogs with cardiac HSA tend to develop pericardial effusion and may display fluid in the abdomen, muffled heart sounds, and weakness.  A high percentage of patients with HSA will also have coagulation abnormalities.  A microangiopathic hemolytic anemia oftentimes results from the presence of HSA causing a decreased platelet count and difficulty in clotting blood.  Disseminated intravascular coagulation (DIC) can occur and must be recognized early and aggressively treated.  Symptoms of DIC in early stages are often minimal, but with more advanced stages can include skin hemorrhages and uncontrollable bleeding. 

How is the diagnosis made? A biopsy is necessary to definitively diagnose HSA.  For skin lesions, surgical removal, if possible, is necessary.  For suspected splenic tumors abdominal ultrasound can identify a mass, but surgical removal of the spleen and the tumor are required.   Cardiac ultrasound (echocardiography) is required to make a presumptive diagnosis of HSA in the heart (usually right atrium or atrial appendage), however a surgical biopsy is required to make a definitive diagnosis.

What staging tests are necessary? Because HSA has a high probability of metastasizing, careful examination of all areas where the cancer has a tendency to spread is critical.  HSA most commonly spreads to the lungs, liver, and heart, so thoracic (chest) radiographs, abdominal ultrasound, and cardiac  ultrasound are recommended.  Pre-operative blood work should include a CBC (complete blood count), serum chemistry panel, coagulation panel (to rule out coagulation abnormalities as described above), and blood typing and cross-matching for possible blood transfusion if surgery is planned in a severely anemic patient. 

 Ultrasound revealed a mass within the spleen of an 11 year old mixed breed dog.  The spleen was removed and fortunately in this case, the diagnosis was extramedullary hematopoiesis, which is benign.  No further treatment was required.

TREATMENT OF HSA:

Surgery: Surgery remains the primary treatment for almost all dogs and cats with HSA. For cutaneous or subcutaneous HSA: aggressive surgical resection to remove all localized tumor tissue is required.  For splenic HSA: splenectomy and careful evaluation of the abdominal cavity at the time of surgery is required.  For primary cardiac HSA , surgery to remove the tumor and concurrent pericardectomy is advised.  The ultrasound picture below is of the heart of a patient with a right atrial tumor.  The white arrows point to the outline of the pericardial sac. The black space in between is the effusion caused by the tumor.  Removing a portion of this sac helps prevent fluid build up. 

Chemotherapy: Survival time post-splenectomy rarely surpasses 3 months due to the high rate of metastasis to the lungs and liver unless chemotherapy is used.   Microscopic disease that is invariably present at the time of surgery is best treated with follow-up chemotherapy. Single agent and combination doxorubicin based chemotherapy protocols are most commonly used.  At ACIC, we recommend single agent doxorubicin (Adriamycin®) given once every 3 weeks for a total of 5-6 treatments.  The reported median survivals for patients with splenic HSA that only undergo surgery is 65 days.  When chemotherapy is used after surgery, median survival times reported in various studies range from 6-10 months.  Other chemotherapy agents have been tried, but survival times have not been improved with other agents.

Metronomic chemotherapy:  Due to the endothelial derivation of HSA, treatments aimed at blood vessel formation (angiogenesis) may offer promising results in the treatment of HSA.  At ACIC we recommend combining low dose chemotherapy (metronomic chemotherapy) in addition to standard doxorubicin chemotherapy.  Metronomic chemotherapy uses traditional chemotherapy drugs in a new way.  Rather than receiving the largest dose of chemotherapy possible, patients undergoing metronomic chemotherapy receive one tenth of the normal dose.  Smaller dosages are less damaging to healthy cells in the body, so chemotherapy can be administered more frequently—sometimes even every day.  The increased frequency of dosing helps prevent the formation of the neoplastic (cancerous) vessels network and as a result prevents the nutrients and oxygen supply from reaching the cancer cells.  A low dose, oral chemotherapy (most commonly cyclophosphamide) in combination with a non-steroidal anti-inflammatory drug (NSAID, e.g. piroxicam) are utilized.   Recent studies in dogs showed that patients treated with metronomic chemotherapy appeared to have similar survivals when compared to dogs treated with standard chemotherapy.  We believe that combining the two methods of treatment may offer a survival advantage over using either one method alone.

Prognosis for non-splenic HSA: Primary cardiac HSA patients that undergo surgery and chemotherapy have similar survival expectations as splenic HSA patients. For cutaneous HSA, survival times are dependent on depth of invasion into the skin and underlying tissue and size of the lesion.  If confined to the superficial skin layer, average survival time with surgery and no chemotherapy is 780 days. As the tumors go deeper into the skin and under the skin, average survival times with surgery alone are 275 days.  Chemotherapy can help prolong patients in this case. In cats, cutaneous lesions more commonly appear and the prognosis is better in subcutaneous lesions if complete surgical excision can be achieved.